This Program Project Grant proposal requests continued support for our investigations to assess and understand magnetic susceptibility effects in NMR, and to use these effects to detect and quantify physiological function. The dynamic effects of high magnetic susceptibility contrast agents are used to measure perfusion. Alterations in endogenous iron compounds are used to measure oxygen consumption. Targeted superparamagnetic iron oxides are used for anatomic and functional imaging. Microscopic variations in susceptibility generate a variety of macroscopic consequences. A coordinated investigation of these effects is proposed, in order to enhance NMR imaging in a variety of organ systems and in disease states, such as cancer and ischemia. Research has been conducted across a wide range of inquiry, including physical, biochemical and physiological mechanisms. This proposal is divided into five research Projects which interact constructively through the use of shared methodology and personnel and through the utilization of common Core resources: NMR brain studies of normal,ischemic and neoplastic tissues based on transient effects of paramagnetic contrast agents and on intrinsic effects of motion in tissue; NMR studies of myocardial perfusion using transient magnetic susceptibility effects, and infarct detection using iron oxide particles attached to antimyosin; NMR image-based assessment of oxygen consumption by measurement of signal changes resulting from intravascular deoxyhemoglobin; Analysis of the macroscopic contrast consequences of microscopic susceptibility variation; Receptor imaging by NMR using a novel contrast agent derived from the binding of monocrystalline iron oxide particles to a variety of biomolecules. The five projects are supported by an Administrative Core and three Core laboratories: the NMR facilities Core; the Computing and Technologies Core; and the High Speed Imaging Core.